Understanding of the role of GABAergic inhibitory interneurons is central to any model of brain function. Interneurons are critical to normal cortical processing and their dysfunction is thought to produce an array of disorders ranging from schizophrenia to epilepsy. Our goal is to understand the role of different classes of interneurons in the functional organization of layers 2/3 of the mouse visual cortex. A better understanding of the functional properties of distinct classes of interneurons may allow targeting of potential therapeutic treatments to specifically ameliorate disease processes. We will apply new techniques to study the physiology of virtually every neuron in a volume of cortex in mice in which distinct subclasses of interneurons are labeled. By combining two-photon calcium imaging and transgenic mouse technology we will address the following Specific Aims: Aim1: We will examine the visual responses of neuronal populations in mouse primary visual cortex. Orientation selectivity, ocular dominance and retinotopy will be measured for thousands of neurons in a volume of layer 2/3. From past work, we expect to find good orientation tuning, but neurons that respond to different orientations will be mixed together. The salt-and-pepper arrangement of orientation implies that there are specific connections among neurons in the local circuit. I propose to study one important aspect of this topic, the role of inhibitory interneurons in such a network. Aim 2: We will examine the receptive-field properties of interneuron subclasses in mouse visual cortex. Two-photon calcium imaging will be applied to existing lines of transgenic mice in which distinct subpopulations of interneurons are labeled. We hypothesize that one class of interneurons (fast-spiking, parvalbumin-positive cells) will be strongly responsive, but non-selective for orientation. Too little is known of other classes, such as low-threshold spiking, somatostatin-positive cells, to make specific predictions about them. But, it is likely that some classes of inhibitory interneurons will have strong stimulus selectivity. The ability to sample large populations of neurons will help characterize rare cell types. More generally, combining comprehensive local circuit physiology with mouse genetics will accelerate our understanding how circuits and their components underlie function and behavior.